Molecular interactions of rifabutin with membrane under acidic conditions

Abstract

This work focuses on the interaction of the anti-tuberculosis (anti-TB) drug, rifabutin (RFB) with cell membrane models formed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). The experiments were performed under acidic conditions (i.e., pH 5.0) taking into account the pH conditions that RFB may find in the course of its in vivo pharmacological activity. The partition of the drug to the membrane was quantified through the partition coefficient (Kp). Fluorescence quenching studies were performed to predict the drug's location across the cell membrane model. The effect of RFB on the biophysical parameters of the cell membrane model was studied by steady-state anisotropy and small-angle X-ray scattering (SAXS). The overall results point to a marked interaction of RFB with cell membranes under acidic pH, which may be related with its pharmacological effects. The in vivo success of RFB may be associated with the drug's disordering effect of the membranes under acidic pH values environments, and consequently drug accumulation in the gastric infected tissues and inside phagolysosomes. On the other hand, the present study allowed establishing important correlations with the gastrointestinal side effects caused by RFB.

Keywords: Drug-membrane studies; Membrane biophysical studies; Membrane models; Rifabutin; Tuberculosis.